Genetic Experts' Views Shift on Testing, Prophylactic Surgery

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Ellen T. Matloff, MS, CGC

The decision about whether to get tested for a genetic mutation that may predispose a person to certain cancers is a difficult one for many patients to make. Even more difficult for mutation carriers is deciding whether to undergo a prophylactic surgical procedure.

How would cancer genetics specialists themselves make these tough choices? Have their perspectives changed over the years, with increased knowledge about genetic testing, surveillance, and treatment?

Ellen T. Matloff, MS, CGC, director of the Yale Cancer Genetic Counseling Program at the Yale School of Medicine/ Yale Cancer Center, in New Haven, Connecticut, shed light on these questions at the 2013 annual meeting of the American College of Medical Genetics and Genomics, held March 19-23 in Phoenix, Arizona. She presented findings of a follow-up survey of 216 active members of the National Society of Genetic Counselors’ Special Interest Group in Cancer.1

“We originally conducted this study in 1998, when cancer genetic testing and counseling was in its infancy, and we had little or no data to tell us what would be the efficacy of prophylactic surgery, surveillance, or chemoprevention for carriers,” explained Matloff.

The follow-up, Internet-based, anonymous survey was conducted in July 2012; male respondents were asked to answer questions as they would for a close female relative.

Much has changed in the 14 years since the 1998 survey—notably, the fact that now 58.3% of the specialists surveyed said that they would opt for bilateral prophylactic mastectomy if they tested positive for a deleterious BRCA mutation at age 35. When that question was asked in 1998, only approximately 25% said that they would choose to have their breasts removed if they were found to be BRCA mutation carriers (Table).

Table. Survey of Cancer Genetic Specialists1

Mutationa

1998b

2012

P Value

BRCA

Would you undergo testing if you had a 50% risk of carrying a mutation?

No 8.1% (n = 13)
Yes 84.5% (n = 136)

No 0.9% (n = 2)
Yes 99.1% (n = 214)

.0006

Would you have your breasts removed if you tested positive for a mutation at age 35?

No 66% (n = 105)
Yes 24.5% (n = 39)

No 41.7% (n = 90)
Yes 58.3% (n = 126)

.0001

HNPCC: If you tested positive for a deleterious mutation at age 35, would you:

Undergo a prophylactic colectomy?

No 61.3% (n = 95)
Yes 17.4% (n = 27)

No 92.6% (n = 200)
Yes 7.4% (n = 16)

.0002

Have your uterus removed prophylactically?

No 28.8% (n = 42)
Yes 54.1% (n = 79)

No 20.4% (n = 44)
Yes 79.6% (n = 172)

.0057

Have your ovaries removed prophylactically?

No 29.7% (n = 43)
Yes 52.4% (n = 76)

No 22.2% (n = 48)
Yes 77.8% (n = 168)

.0090

aMale respondents were asked to answer as they would for a close female relative.bNumbers do not add up to 100% because not all participants answered all questions.

Decreased risk (57.9%) and avoidance of fear/worry (49.1%) were cited most often by respondents who said they would choose mastectomy if found to be mutation carriers. Twelve percent indicated that a lack of confidence in surveillance would be a factor in their decision to have their breasts removed.

“This was a very controversial issue in 1998, and it still is to some extent in 2012,” said Matloff. Those who would choose not to have the prophylactic procedure listed confidence in surveillance (33.3%), negative impact of surgery on body image and sexuality (22.2%), and the fact that the surgery would not provide 100% protection against recurrence (10.6%).

On the question of whether to undergo BRCA testing if risk for the mutation was determined to be 50%, a large majority of respondents to both surveys said that they would choose to be tested: 84.5% of those responding to the 1998 survey and all but two of the respondents in 2012 (99.1%). Among the reasons 2012 respondents gave for choosing to be tested were that the information would aid in medical management, it would be helpful to their families, and it would lessen uncertainty; 55.6% of the affirmative respondents said they would choose to be tested for the 50% probability that they would test negative.

Matloff added that she did not present data on whether BRCA mutation carriers would have their ovaries removed, because the percentage was high in both surveys and not statistically significant.

The researchers also found statistically significant differences in attitudes toward prophylactic surgery for Lynch syndrome between the two surveys. When asked if they would choose prophylactic colectomy if positive for a deleterious HNPCC mutation at age 35, only 16 respondents to the 2012 survey (7.4%) said they would, compared with 27 people (17.4%) who answered affirmatively in 1998. Respondents in 2012 indicated confidence in colonoscopy, lowered quality of life and body image, and a willingness to postpone surgery until detection of a lesion or polyp as reasons for this choice.

However, when the same question was asked with regard to removal of the uterus or ovaries due to an elevated Lynch syndrome risk, participants were more inclined to respond affirmatively. Nearly 80% of 2012 respondents said they would have their uterus removed if found to carry the HNPCC mutation at age 35, compared with 54.1% in 1998. Similarly, nearly 78% of respondents in 2012 indicated that they would have their ovaries removed versus 52.4% in 1998.

The survey also explored the issue of anonymity in genetic testing with respect to health insurance, and the results indicate that respondents are for the most part confident that billing their insurance company for testing would not be detrimental, with 94.9% of the 2012 respondents replying that they would, compared with just 23.9% in 1998.

“I find this particularly interesting because I’m not sure we would even think to ask these questions in 2012, but these were top of mind in 1998,” Matloff observed.

Matloff explained that gauging the perspectives of experts on issues related to genetic testing and possible interventions is especially important, insofar as the specialists surveyed “arguably have the most education and clinical experience in cancer genetic counseling and testing.”

“We now know that genetic testing is well established, as compared with 1998, and that more clinicians know about BRCA and Lynch syndrome,” said Matloff. She added that more clinicians are treating patients who carry mutations, and they can see both the natural progression of disease and also the stress inherent for people who test positive, as well as the stress among unaffected carriers, as they undergo surveillance, chemoprevention, and prophylactic surgery.